Over the last few decades, advances in the management of acute myocardial infarction (MI) have resulted in an impressive 40% reduction in mortality during the acute phase. However, despite these results, the development of late-onset heart failure following MI has not significantly decreased and remains associated with a more than 10-fold elevated risk of death. A better understanding of the factors involved in the development of late-onset heart failure will help to identify high-risk patients more likely to benefit from an intervention (Ref. 1-4).
Until recently, the initial laboratory evaluation of patients presenting myocardial infarction consisted entirely of creatine kinase (CK) and troponin measurements. Both are sensitive markers of myocardial injury and there is a reasonably good correlation between levels of CK and size of infarction in the absence of reperfusion. However, both markers are largely affected by a wash out phenomenon during reperfusion, which makes the interpretation of the markers difficult in the setting of thrombolysis and primary angioplasty/stenting, which are now the preferred mode of treatment of the majority of the patients with acute MI. Indeed, the relationship between levels of CK/troponin and the size of infarction or the risk for future cardiac events such as heart failure is inconsistent.
Several markers of inflammation such as high-sensitivity C-reactive protein (hs-CRP), soluble CD40 ligand and myeloperoxidase have been found to be independent predictors of death or nonfatal myocardial infarction at 6 months among patients presenting acute coronary syndromes. However, those markers have not been associated with the development of heart failure post MI. B-type natriuretic peptide (BNP) is a cardiac neurohormone that is elevated in response to left ventricular pressure overload. BNP is increasingly being recognized as an important prognostic marker in patients with heart failure and acute MI. The usefulness of BNP determination in the acute phase of MI is limited by rapid fluctuations in peptide levels during the first 24 hours of MI. BNP levels are also affected by numerous co-morbidities such as chronic obstructive lung disease and renal insufficiency.
The future management of patients with acute MI receiving reperfusion therapy with thrombolysis or primary angioplasty/stenting requires a strategy to more accurately risk-stratify patients and guide treatment. Accordingly it is an object of the present invention to provide a new technique for identifying subjects at risk of developing heart failure following a MI.